The Japanese Society of Pathology Practical Guidelines on the handling of pathological tissue samples for cancer genomic medicine.

Clinical cancer genomic testing based on next-generation sequencing can help select genotype-matched therapy and provide diagnostic and prognostic information. Pathological tissue from malignant tumors obtained during routine practice are frequently used for genomic testing. This article is aimed to standardize the proper handling of pathological specimens in practice for genomic medicine based on the findings established in "Guidelines on the handling of pathological tissue samples for genomic medicine (in Japanese)" published by The Japanese Society of Pathology (JSP) in 2018. The two-part practical guidelines are based on empirical data analyses; Part 1 describes the standard preanalytic operating procedures for tissue collection, processing, and storage of formalin-fixed paraffin-embedded (FFPE) samples, while Part 2 describes the assessment and selection of FFPE samples appropriate for genomic testing, typically conducted by a pathologist. The guidelines recommend that FFPE sample blocks be used within 3 years from preparation, and the tumor content should be ≥30% (minimum 20%). The empirical data were obtained from clinical studies performed by the JSP in collaboration with leading Japanese cancer genome research projects. The Japanese Ministry of Health, Labour, and Welfare (MHLW) recommended to comply with the JSP practical guidelines in implementing cancer genomic testing under the national health insurance system in over 200 MHLW-designated core and cooperative cancer genome medicine hospitals in Japan.

Archival bone marrow smears are useful in targeted next-generation sequencing for diagnosing myeloid neoplasms.

Gene abnormalities, including mutations and fusions, are important determinants in the molecular diagnosis of myeloid neoplasms. The use of bone marrow (BM) smears as a source of DNA and RNA for next-generation sequencing (NGS) enables molecular diagnosis to be done with small amounts of bone marrow and is especially useful for patients without stocked cells, DNA or RNA. The present study aimed to analyze the quality of DNA and RNA derived from smear samples and the utility of NGS for diagnosing myeloid neoplasms. Targeted DNA sequencing using paired BM cells and smears yielded sequencing data of adequate quality for variant calling. The detected variants were analyzed using the bioinformatics approach to detect mutations reliably and increase sensitivity. Noise deriving from variants with extremely low variant allele frequency (VAF) was detected in smear sample data and removed by filtering. Consequently, various driver gene mutations were detected across a wide range of allele frequencies in patients with myeloid neoplasms. Moreover, targeted RNA sequencing successfully detected fusion genes using smear-derived, very low-quality RNA, even in a patient with a normal karyotype. These findings demonstrated that smear samples can be used for clinical molecular diagnosis with adequate noise-reduction methods even if the DNA and RNA quality is inferior.

From Operating Table to Laboratory Bench: The Path Toward Metastasis Research from the Clinical Setting.

Presence of metastasis translates unequivocally into worse prognosis for our patients. Translational medicine has been our response to offer patients better therapeutic options. This chapter aims to provide an overview for clinicians to send the necessary metastatic tissue on the right path toward the laboratory bench, overcoming biases and possible data misinterpretations derived from poor sample quality.

Evolution of a Novel Tissue Preservation Protocol to Optimize Osteochondral Transplantation Outcomes.

OBJECTIVE: Osteochondral allograft transplantation is a procedure to treat focal osteochondral lesions (OCLs), but is limited by tissue availability, the quality of transplanted tissue, and inconsistent storage protocols. The objective of this study was to assess the clinical outcomes of a novel tissue procurement, storage, and quality control protocol in treating OCLs. DESIGN: Prospective case series. Donor cadaveric tissue was processed, stored, and the tissue quality analyzed using the unique tissue preservation protocol developed at our institution. Advanced cross-sectional imaging was used to size match donor tissue with recipient patients. Osteochondral allografts were transplanted using the Arthrex Allograft OATS. Patients were evaluated with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee injury and Osteoarthritis Outcome Score (KOOS), visual analog scale (VAS), and 36-Item Short Form Survey (SF-36) preoperatively and at 1 year and 2 years postoperatively. RESULTS: Twenty patients (17 knees, 3 shoulders) were included in the study. There was a significant improvement in the following scores: overall WOMAC score, WOMAC function and pain subcategories; KOOS pain, knee-related symptoms, activities of daily living, sports and recreation, and quality of life; SF-36 physical functioning, physical role, pain, and social functioning subcategories; and VAS at all time points postoperatively. There was a significant improvement in WOMAC stiffness at 2 years postoperatively. There were 2 failures, defined by graft subsidence and persistent pain requiring reoperation. CONCLUSION: The protocol developed at our institution for OAT resulted in significant clinical improvement in patients with OCLs and is an improvement on existing tissue storage techniques.

Progenitor Biological Bandages: An Authentic Swiss Tool for Safe Therapeutic Management of Burns, Ulcers, and Donor Site Grafts.

Clinical experience gathered over two decades around therapeutic use of primary human dermal progenitor fibroblasts in burn patient populations has been at the forefront of regenerative medicine in Switzerland. Relative technical simplicity, ease of extensive serial multitiered banking, and high stability are major advantages of such cell types, assorted to ease of safety and traceability demonstration. Stringent optimization of cell source selection and standardization of biobanking protocols enables the safe and efficient harnessing of the considerable allogenic therapeutic potential yielded by primary progenitor cells. Swiss legal and regulatory requirements have led to the procurement of fetal tissues within a devised Fetal Progenitor Cell Transplantation Program in the Lausanne University Hospital. Proprietary nonenzymatic isolation of primary musculoskeletal cell types and subsequent establishment of progeny tiered cell banks under cGMP standards have enabled safe and effective management of acute and chronic cutaneous affections in various patient populations. Direct off-the-freezer seeding of viable dermal progenitor fibroblasts on a CE marked equine collagen scaffold is the current standard for delivery of the therapeutic biological materials to patients suffering from extensive and deep burns. Diversification in the clinical indications and delivery methods for these progenitor cells has produced excellent results for treatment of persistent ulcers, autograft donor site wounds, or chronic cutaneous affections such as eczema. Herein we describe the standard operating procedures for preparation and therapeutic deployment of the progenitor biological bandages within our translational musculoskeletal regenerative medicine program, as they are routinely used as adjuvants in our Burn Center to treat critically ailing patients.

GMP Tiered Cell Banking of Non-enzymatically Isolated Dermal Progenitor Fibroblasts for Allogenic Regenerative Medicine.

Non-enzymatically isolated primary dermal progenitor fibroblasts derived from fetal organ donations are ideal cell types for allogenic musculoskeletal regenerative therapeutic applications. These cell types are differentiated, highly proliferative in standard in vitro culture conditions and extremely stable throughout their defined lifespans. Technical simplicity, robustness of bioprocessing and relatively small therapeutic dose requirements enable pragmatic and efficient production of clinical progenitor fibroblast lots under cGMP standards. Herein we describe optimized and standardized monolayer culture expansion protocols using dermal progenitor fibroblasts isolated under a Fetal Transplantation Program for the establishment of GMP tiered Master, Working and End of Production cryopreserved Cell Banks. Safety, stability and quality parameters are assessed through stringent testing of progeny biological materials, in view of clinical application to human patients suffering from diverse cutaneous chronic and acute affections. These methods and approaches, coupled to adequate cell source optimization, enable the obtention of a virtually limitless source of highly consistent and safe biological therapeutic material to be used for innovative regenerative medicine applications.

GMP-Grade Methods for Cardiac Progenitor Cells: Cell Bank Production and Quality Control.

Cardiac explant-derived cells (cEDC), also referred as cardiac progenitors cells (CPC) (Barile et al., Cardiovasc Res 103(4):530-541, 2014; Barile et al., Cardiovasc Res 114(7):992-1005, 2018), represent promising candidates for the development of cell-based therapies, a novel and interesting treatment for cardioprotective strategy in heart failure (Kreke et al., Expert Rev Cardiovasc Ther 10(9):1185-1194, 2012). CPC have been tested in a preclinical setting for direct cell transplantation and tissue engineering or as a source for production of extracellular vesicles (EV) (Oh et al., J Cardiol 68(5):361-367, 2016; Barile et al., Eur Heart J 38(18):1372-1379, 2017; Rosen et al., J Am Coll Cardiol 64(9):922-937, 2014). CPC cultured as cardiospheres derived cells went through favorable Phase 1 and 2 studies demonstrating safety and possible efficacy (Makkar et al., Lancet 379(9819):895-904, 2012; Ishigami et al., Circ Res 120(7):1162-1173, 2017; Ishigami et al., Circ Res 116 (4):653-664, 2015; Tarui et al., J Thorac Cardiovasc Surg 150(5):1198-1207, 1208 e1191-1192, 2015). In this context and in view of clinical applications, cells have to be prepared and released according to Good Manufacturing Practices (GMP) (EudraLex-volume 4-good manufacturing practice (GMP) guidelines-Part I-basic requirements for medicinal products. http://ec.europa.eu/health/documents/eudralex/vol-4 ; EudraLex-volume 4-good manufacturing practice (GMP) guidelines-Part IV-guidelines on good manufacturing practices specific to advanced therapy medicinal products. http://ec.europa.eu/health/documents/eudralex/vol-4 ). This chapter describes GMP-grade methods for production and testing of a CPC Master Cell Bank (MCB), consisting of frozen aliquots of cells that may be used either as a therapeutic product or as source for the manufacturing of Exo for clinical trials.The MCB production method has been designed to isolate and expand CPC from human cardiac tissue in xeno-free conditions (Andriolo et al., Front Physiol 9:1169, 2018). The quality control (QC) methods have been implemented to assess the safety (sterility, endotoxin, mycoplasma, cell senescence, tumorigenicity) and identity/potency/purity (cell count and viability, RT-PCR, immunophenotype) of the cells (Andriolo et al., Front Physiol 9:1169, 2018).

Replantation of two avulsed teeth after 1 h of storage in adverse extraoral dry conditions: A thought-provoking outcome after a 15-month follow-up.

This article reports a clinical case of an 8-year-old boy who sustained avulsion of the maxillary right central incisor and the maxillary left lateral incisor. The avulsed teeth were kept in adverse extraoral dry conditions for 1 h from the moment of trauma until their replantation. The prognosis of tooth replantation is dependent on multiple factors such as methods of teeth storage in vitro, endodontic intervention, extra-oral time, and type of retention employed. The main reasons for root resorption in this case may be the extra-oral time, the initial replantation, or the delayed endodontic treatment.

Therapeutic Utility of Cold-Stored Platelets or Cold-Stored Whole Blood for the Bleeding Hematology-Oncology Patient.

Bleeding related to thrombocytopenia is common in hematology-oncology patients. Platelets stored at room temperature (RTPs) are the current standard of care. Platelets stored in the cold (CSPs) have enhanced hemostatic function relative to RTPs. CSPs were reported to reduce bleeding in hematology-oncology patients. Recent studies have confirmed the enhanced hemostatic properties of CSPs. CSPs may be the better therapeutic option for this population. CSPs may also offer a preferable immune profile, reduced thrombotic risk, and reduced transfusion-transmitted infection risk. The logistical advantages of CSPs would improve outcomes for many patients who currently cannot access platelet transfusions.

[Comparative normative on sanitary practices of cadaveric preservation in Spain]. / Normativa comparada sobre prácticas sanitarias de conservación cadavérica en Españ.

In this paper the current regulations on cadaveric preservation practices required for the transfer of corpses in the different Autonomous Communities -Reglamentos de Policía Sanitaria Mortuoria- and national legislation are compared. The criteria taken into account have been: a) which sanitary practices are included in the regulations, b) which ones can be carried out in corpses posing a health risk, c) when they are compulsory to be carried out, d) when they can be carried out after death, and e) what professionals can carry them out and/or take responsibility for them. At the time of finishing the paper, a new mortuary regulation is being passed in Andalusia, as well as a decree from the Ministry of Health on technical and sanitary requirements concerning international transfer of corpses and human remains.

Se comparan las normativas vigentes sobre prácticas sanitarias de conservación cadavérica requeridas para el traslado de cadáveres, en las diferentes Comunidades autónomas y la legislación estatal. Los criterios tenidos en cuenta han sido: qué prácticas sanitarias se incluyen en la normativa, cuáles pueden llevarse a cabo en cadáveres de riesgo sanitario, cuándo se requiere su realización, en qué momento tras el fallecimiento pueden realizarse y qué profesionales las pueden llevarlas a cabo y/o responsabilizarse de las mismas. En el momento de finalizar el artículo se está tramitando la publicación del nuevo decreto de sanidad mortuoria de Andalucía, así mismo se está elaborando, por parte del Ministerio de Sanidad, Consumo y Bienestar Social, un Real Decreto sobre "Condiciones técnico sanitarias básicas en materia de traslado internacional de cadáveres, restos humanos y restos cadavéricos".

Normativa comparada sobre prácticas sanitarias de conservación cadavérica en España / Comparative normative on sanitary practices of cadaveric preservation in Spain

Se comparan las normativas vigentes sobre prácticas sanitarias de conservación cadavérica requeridas para el traslado de cadáveres, en las diferentes Comunidades autónomas y la legislación estatal. Los criterios tenidos en cuenta han sido: qué prácticas sanitarias se incluyen en la normativa, cuáles pueden llevarse a cabo en cadáveres de riesgo sanitario, cuándo se requiere su realización, en qué momento tras el fallecimiento pueden realizarse y qué profesionales las pueden llevarlas a cabo y/o responsabilizarse de las mismas. En el momento de finalizar el artículo se está tramitando la publicación del nuevo decreto de sanidad mortuoria de Andalucía, así mismo se está elaborando, por parte del Ministerio de Sanidad, Consumo y Bienestar Social, un Real Decreto sobre "Condiciones técnico sanitarias básicas en materia de traslado internacional de cadáveres, restos humanos y restos cadavéricos"

In this paper the current regulations on cadaveric preservation practices required for the transfer of corpses in the different Autonomous Communities -Reglamentos de Policía Sanitaria Mortuoria- and national legislation are compared. The criteria taken into account have been: a) which sanitary practices are included in the regulations, b) which ones can be carried out in corpses posing a health risk, c) when they are compulsory to be carried out, d) when they can be carried out after death, and e) what professionals can carry them out and/or take responsibility for them. At the time of finishing the paper, a new mortuary regulation is being passed in Andalusia, as well as a decree from the Ministry of Health on technical and sanitary requirements concerning international transfer of corpses and human remains

Análisis de la relación solicitud-implante de injerto para trasplante osteomuscular / Analysis of the order-implantation relationship for musculoskeletal tissue transplantation

Objetivo: Analizar los pedidos solicitados a un banco musculoesquelético y evaluar el porcentaje de utilización de los tejidos. Material y métodos: Se analizaron 265 pedidos de tejido osteomuscular en el transcurso de un año. Exclusiones: 5 duplicaciones y 5 pedidos en los cuales no hubo disponibilidad para cubrir la necesidad. Se analizó la cantidad de cirugías en las que finalmente se utilizó el injerto. Resultados: De 255 pedidos solicitados, en 178 (70%) el injerto fue utilizado, mientras que en 77 (30%) el injerto no fue utilizado. De los 178 utilizados, en 23 (10%) hubo una devolución parcial. De los 77 pedidos de injerto no utilizado, en 32 (13%) la cirugía fue realizada sin necesidad de utilizar tejido de banco, mientras que en los 45 (17%) restantes la cirugía fue suspendida. Discusión: Un 30% de los injertos solicitados no fueron utilizados; un 17% debido a que la cirugía fue suspendida y un 13% porque el tejido fue devuelto, ya que la cirugía no lo requirió. En otro 10% hubo una devolución parcial del tejido. Con base en este análisis, consideramos que es importante tener una confirmación directa de la realización de la cirugía para evitar enviar tejido a cirugías suspendidas, ya que además del impacto económico, el banco debe asegurar un adecuado mantenimiento de la temperatura durante el transporte y almacenamiento en el centro trasplantológico, para evitar el descarte de dicho tejido, en caso de ser devuelto

Objective: To analyze orders requested from a musculoskeletal tissue bank and to evaluate the percentage of tissue implantation. Material and methods: Two hundred and sixty-five orders for musculoskeletal tissue were analyzed over the course of a year. Exclusions: 5 duplications and 5 orders for which there was no availability to cover the need. We analyzed the number of surgeries in which the graft was finally used. Results: Of a total of 255 orders, the graft was used in 178 (70%), and the graft was not used in 77 (30%). Of the 178 used, there was a partial refund in 23 (10%). Of the 77 orders not used, surgery was performed in 32 (13%) without the use of bank tissue, while surgery was discontinued in the remaining 45 (17%). Discussion: A non-utilization rate of 30% was identified, of which 17% was from surgery that was not performed and 13% from surgery that was performed, but the tissue was returned to the tissue bank, because it was not required. In a further 10% there was partial return of the tissue. Based on this analysis, we consider that it is important to have direct confirmation of the surgery to avoid sending tissue for discontinued surgeries, since in addition to the economic impact, the bank must ensure adequate temperature maintenance during transportation and storage in the transplantation centre, to avoid discarding said tissue if it is returned

Endothelial assessment of donated tectonic corneas: a viable option for posterior lamellar transplantation.

PURPOSE: Donated corneas are classified as tectonic if there are defects within any layers of the cornea which would prevent a satisfactory visual outcome after transplantation. This study aimed to evaluate whether some tectonic corneas have sufficient endothelial characteristics to allow their use in posterior lamellar keratoplasty, and explored their reclassification for use in this sight-improving procedure. METHODS: A retrospective review of all corneal tissues preserved by the Sorocaba Eye Bank from January to April of 2014 was performed. All donated corneas classified as tectonic were included. Endothelial tissue was defined as healthy and viable for posterior lamellar keratoplasty if endothelial cell density was ≥2000 cells/mm2. Additional parameters analyzed included Descemet folds and stretch marks, loss of endothelial cells, corneal endothelial polymegathism/ pleomorphism, pseudo-guttata, and reflectivity. RESULTS: During the study period, 2,847 corneas were preserved, of which 423 (14.85%) were classified as tectonic. Of these, 87 (20.56%) were reported as having endothelial viability and were included in the posterior lamellar keratoplasty group. Average corneal endothelial cell density of this group was 2,471 SD ± 256 cells/mm2 (range 2012-2967 cells/mm2). CONCLUSION: A significant number of corneas classified as tectonic showed endothelial viability and were included in the posterior lamellar keratoplasty group (20.56%). Despite stromal and/or epithelial alterations, these corneas could have been potentially distributed for posterior lamellar transplantation to improve vision, thus reducing the corneal transplantation waiting period. This study highlights how corneal tissue reclassification could increase the potential amount of corneal tissue available for optical transplantation.

Endothelial assessment of donated tectonic corneas: a viable option for posterior lamellar transplantation / Avaliação da viabilidade do uso de córneas tectônicas em transplantes lamelares posteriores a partir da análise da vitalidade das células endoteliais

ABSTRACT Purpose: Donated corneas are classified as tectonic if there are defects within any layers of the cornea which would prevent a satisfactory visual outcome after transplantation. This study aimed to evaluate whether some tectonic corneas have sufficient endothelial characteristics to allow their use in posterior lamellar keratoplasty, and explored their reclassification for use in this sight-improving procedure. Methods: A retrospective review of all corneal tissues preserved by the Sorocaba Eye Bank from January to April of 2014 was performed. All donated corneas classified as tectonic were included. Endothelial tissue was defined as healthy and viable for posterior lamellar keratoplasty if endothelial cell density was ≥2000 cells/mm2. Additional parameters analyzed included Descemet folds and stretch marks, loss of endothelial cells, corneal endothelial polymegathism/ pleomorphism, pseudo-guttata, and reflectivity. Results: During the study period, 2,847 corneas were preserved, of which 423 (14.85%) were classified as tectonic. Of these, 87 (20.56%) were reported as having endothelial viability and were included in the posterior lamellar keratoplasty group. Average corneal endothelial cell density of this group was 2,471 SD ± 256 cells/mm2 (range 2012-2967 cells/mm2). Conclusion: A significant number of corneas classified as tectonic showed endothelial viability and were included in the posterior lamellar keratoplasty group (20.56%). Despite stromal and/or epithelial alterations, these corneas could have been potentially distributed for posterior lamellar transplantation to improve vision, thus reducing the corneal transplantation waiting period. This study highlights how corneal tissue reclassification could increase the potential amount of corneal tissue available for optical transplantation.

RESUMO Objetivo: Avaliar a vitalidade endotelial das córneas classificadas como tectônicas e discutir a viabilidade de seu uso na ceratoplastia lamelar posterior. Métodos: Realizou-se uma revisão retrospectiva de todos os tecidos corneanos preservados pelo Banco de Olhos Sorocaba de janeiro a abril de 2014. Todas as córneas doadas classificadas como tectônicas foram incluídas e avaliadas com ênfase na vitalidade endotelial. Os parâmetros de avaliação da lâmpada de fenda de cada córnea e densidade de células endoteliais medidos por microscópio especular foram registrados: córneas que apresentavam vitalidade endotelial apesar de alterações no estroma e/ou no epitélio foram selecionadas e incluídas em um grupo denominado grupo lamelar posterior. O tecido endotelial foi definido como saudável e viável para a ceratoplastia lamelar posterior, se houvesse uma densidade de células endoteliais ≥2.000 células/mm2. Outros parâmetros também foram analisados, incluindo; estrias ou pregas na Descemet, perda de células endoteliais, polimegatismo e pleomorfismo endotelial, pseudo-guttata e reflexividade endotelial. Resultados: Durante o período do estudo, foram preservadas 2.847 córneas, das quais 423 (14,85%) foram classificadas como tectônicas. Dessas, 87 (20,56%) apresentaram vitalidade endotelial e foram incluídos no grupo lamelar posterior. A densidade média das células endoteliais da córnea deste grupo era de 2.471 SD ± 256 células/mm2, variando de 2.012 a 2.967 células/mm2. Conclusão: Um número significativo de córneas classificadas como tectônicas apresentaram vitalidade endotelial e foram incluídas no grupo lamelar posterior (20,56%). Apesar de alterações estromais e/ou epiteliais, estas córneas poderiam ter sido potencialmente distribuídas para transplantes lamelares posteriores com finalidade ótica, otimizando a disponibilidade de tecidos, com impacto positivo na saúde pública.

CT checklist and scoring system for the assessment of soft tissue preservation in human mummies: application to catacomb mummies from Palermo, Sicily.

In this study we applied the recently developed "Checklist and Scoring System for the Assessment of Soft Tissue Preservation in Human Mummies" to catacomb mummies from Palermo, Sicily. Data from twenty-three full-body computed tomography (CT) examinations were available. These consisted of seventeen adults and six children dating from the late 18th to the late 19th centuries AD. Seventeen of these mummies were anthropogenically mummified, and six spontaneously. Based on the checklist and scoring system, soft tissue preservation varied between both mummification groups, among mummies with the same type of mummification, and within individual mummies at different anatomical locations. Checkpoints of the main category "A. Soft Tissues of Head and Musculoskeletal System" were clearly more frequent than checkpoints of the main category "B. Organs and Organ Systems". Among the anthropogenic mummies, intra-arterial filling achieved the highest preservation status of organs and organ systems. Despite the small sample size, the statistical evaluation showed significant differences between mummification types, with the highest soft tissue preservation found in anthropogenic mummies. Application of the "Checklist" allowed a standardized assessment and documentation of the soft tissue preservation of these mummies. The "Scoring System" facilitated a comparison among mummification groups and mummies by means of numeric values.

Effect of in vitro storage duration on measured mechanical properties of brain tissue.

Accurate characterization of the mechanical properties of brain tissue is essential for understanding the mechanisms of traumatic brain injuries and developing protective gears or facilities. However, how storage conditions might affect the mechanical properties of brain tissue remains unclear. The objective of this study is to investigate the effect of in vitro storage duration on the mechanical performance of brain tissue since measurements are usually carried out in vitro. Differential Scanning Calorimetry (DSC) measurements and uniaxial compression mechanical experiments are carried out. The results indicate that, for brain tissue stored at 1 °C without any liquid medium, the bio-molecular interactions and the mechanical strength of both white and grey matter deteriorate with prolonged storage duration. Transmission Electron Microscopy (TEM) results reveal the degeneration of myelin sheaths and the vacuolization of cristae with prolonged storage duration, suggesting that the in vitro storage duration should be carefully controlled. The findings from this study might facilitate the development of guidelines and standards for the in vitro storage of brain tissue.

Organ donation and transplantation: Awareness and roles of healthcare professionals-A systematic literature review.

AIMS AND OBJECTIVES: To examine the role of healthcare professionals in the organ donation and transplantation process. BACKGROUND: Globally, there remains a perennial disequilibrium between organ donation and organ transplantation. Several factors account for this disequilibrium; however, as healthcare professionals are not only strategically positioned as the primary intermediaries between organ donors and transplant recipients, but also professionally situated as the implementers of organ donation and transplantation processes, they are often blamed for the global organ shortage. DESIGN: Mixed-method systematic review using the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols 2015 checklist. METHODS: Databases were searched including CINAHL, MEDLINE, Web of Science and EMBASE using the search terms "organ donation," "healthcare professionals," "awareness" and "roles" to retrieve relevant publications. RESULTS: Thirteen publications met the inclusion criteria. The global organ shortage is neither contingent upon unavailability of suitable organs nor exclusively dependent upon healthcare professionals. Instead, the existence of disequilibrium between organ donation and transplantation is necessitated by a web of factors. These include the following: healthcare professionals' attitudes towards, and experience of, the organ donation and transplantation process, underpinned by professional education, specialist clinical area and duration of professional practice; conflicts of interests; ethical dilemmas; altruistic values towards organ donation; and varied organ donation legislations in different legal jurisdictions. CONCLUSION: This review maintains that if this web of factors is to be adequately addressed by healthcare systems in different global and legal jurisdictions, there should be sufficient organs voluntarily donated to meet all transplantation needs. RELEVANCE TO CLINICAL PRACTICE: There is a suggestion that healthcare professionals partly account for the global shortage in organ donation, but there is a need to examine how healthcare professionals' roles, knowledge, awareness, skills and competencies might impact upon the organ donation and transplantation process.

[Bone banks : The state-of-the-art]. / Knochenbanken : State-of-the-Art.

Bone banks are responsible for the collection, production, testing, packaging, storage and delivery of osseous grafts. In compliance with legal and quality requirements, it is their main task to ensure the biological properties and the microbiological safety of the transplants as well. German legal requirements for bone banking are explained and current standards with respect to donor selection, laboratory tests and tissue processing, as well as labeling are discussed. Production and preparation procedures should include a validated microbiological inactivation method that largely preserves the biological properties of the tissue.